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Malignant Otitis Externa: Evolving Pathogens and Implications for Diagnosis and Treatment
Candace E. Hobson, Jennifer D. Moy, Karin E. Byers, Yael Raz, Barry E. Hirsch and Andrew A. McCall
Otolaryngology -- Head and Neck Surgery published online 26 March 2014
DOI: 10.1177/0194599814528301

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Original Research
Malignant Otitis Externa: Evolving
Pathogens and Implications for Diagnosis
and Treatment
Candace E. Hobson, MD1, Jennifer D. Moy, MD1,
Karin E. Byers, MD2, Yael Raz, MD1, Barry E. Hirsch, MD1, and
Andrew A. McCall, MD1
No sponsorships or competing interests have been disclosed for this article.
Abstract
Objective. Malignant otitis externa (MOE) is an invasive infection
of the temporal bone that is classically caused by Pseudomonas
aeruginosa. Increasingly, however, nonpseudomonal cases are
being reported. The goal of this study was to evaluate and com-
pare the clinical presentation and outcomes of cases of MOE
caused by Pseudomonas versus non-Pseudomonas organisms.
Study Design. Retrospective case series with chart review.
Setting. Tertiary care institution.
Subjects and Methods. Adult patients with diagnoses of MOE
between 1995 and 2012 were identified. Charts were
reviewed for history, clinical presentation, laboratory data,
treatment, and outcomes.
Results. Twenty patients diagnosed with and treated for MOE
at the University of Pittsburgh Medical Center between 1995
and 2012 were identified. Nine patients (45%) had cultures
that grew P aeruginosa. Three patients (15%) had cultures that
grew methicillin-resistant Staphylococcus aureus (MRSA). Signs
and symptoms at presentation were similar across groups.
However, all of the patients with Pseudomonas had diabetes,
compared with 33% of MRSA-infected patients (P = .046) and
55% of all non-Pseudomonas-infected patients (P = .04).
Patients infected with MRSA were treated for an average total
of 4.7 more weeks of antibiotic therapy than Pseudomonas-
infected patients (P = .10). Overall, patients with non-
Pseudomonas infections were treated for a total of 2.4 more
weeks than Pseudomonas-infected patients (P = .25).
Conclusions. A high index of suspicion for nonpseudomonal
organisms should be maintained in patients with signs and
symptoms of MOE, especially in those without diabetes.
MRSA is an increasingly implicated organism in MOE.
Keywords
malignant otitis externa, necrotizing otitis externa, methicillin-
resistant Staphylococcus aureus, MRSA, Pseudomonas aerugi-
nosa, otitis externa
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Otolaryngology–
Head and Neck Surgery
1–5
Ó American Academy of
Otolaryngology—Head and Neck
Surgery Foundation 2014
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DOI: 10.1177/0194599814528301
http://otojournal.org
Received September 3, 2013; revised January 16, 2014; accepted
February 26, 2014.
Introduction
Malignant otitis externa (MOE) is a potentially life-threatening
osteomyelitis of the temporal bone that can extend to involve
the surrounding soft tissues, cranial nerves, and adjacent skull
base. Elderly, diabetic, or immunocompromised patients are
most frequently afflicted. In 1959, Meltzer and Kelemen1 first
described this infection in a case report of a patient with dia-
betes with fatal temporal bone osteomyelitis that originated
from otitis externa. Cultures from their patient’s ear grew
Bacillus pyocyanea, which is now known as Pseudomonas
aeruginosa. In 1968, Chandler2 coined the term ‘‘malig-
nant otitis externa’’ to describe this morbid pseudomonal
infection. Since then, the presence of Pseudomonas in
affected ears has been thought to be one of the hallmark
features of this disease.3
It was not until 1982 that the first case of nonpseudomonal
MOE was reported. In that report, Bayardelle et al4 described
a case of MOE due to oxacillin-sensitive Staphylococcus
aureus. Since then, there have been multiple reports of S
aureus as the sole offending organism in MOE.5,6 There have
been few reports of methicillin-resistant S aureus (MRSA) as
the causative pathogen in MOE7,8; however, the overall inci-
dence of MRSA skin and soft tissue infections has been rising
steadily.9 Additionally, although earlier reports revealed P aer-
uginosa as the causative organism in most cases of MOE,
1
Department of Otolaryngology, University of Pittsburgh Medical Center,
Pittsburgh, Pennsylvania, USA
2
Department of Medicine, Division of Infectious Diseases, University of
Pittsburgh Medical Center, Pittsburgh, Pennsylvania, USA
This article was presented as a poster at the 2013 AAO-HNSF Annual
Meeting & OTO EXPO; September 29 to October 3, 2013; Vancouver,
British Columbia, Canada.
Corresponding Author:
Andrew A. McCall, University of Pittsburgh, Department of
Otolaryngology–Head and Neck Surgery, 203 Lothrop Street, Suite 500,
Pittsburgh, PA 15213, USA
Email: mccallaa@upmc.edu
2 Otolaryngology–Head and Neck Surgery

Table 1. Pathogens and Clinical Features.

All Patients Pseudomonas MRSA Other Negative
Clinical Feature (n = 20) (n = 9) (n = 3) (n = 5) (n = 3)

Percentage of patients 100 45 15 25 15

Average age (y) 64.9 62.3 63.0 65.0 74.3
Age range (y) 42-100 42-77 44-100 52-79 61-84
Diabetes mellitus 75% 100.0% 33.3% 80.0% 33.3%
Facial nerve palsy 25% 33.3% 0% 20% 33.3%
Bony erosion (on CT scan) 95% 100% 100% 100% 66.7%
Failed local treatment 80% 66.7% 100% 80% 100%
Definitive therapy (wk) 7.8 6.1 8.5 11.8 6.7
Total therapy (wk) 9.2 7.9 12.6 12.0 6.7
Abbreviations: CT, computed tomographic; MRSA, methicillin-resistant Staphylococcus aureus.

more recent reports have documented Pseudomonas infection
less frequently, with Pseudomonas cultured in as few as 27%
to 54% of cases.5-7
Given the increasing frequency of nonpseudomonal
MOE, we decided to retrospectively review our clinical
experience with MOE and specifically compare clinical pre-
sentations, management, and outcomes of this infection
between cases caused by Pseudomonas and MRSA. We
hypothesized that the clinical presentation would be similar,
regardless of the causative organism, and that treatment
might be prolonged when caused by MRSA or other non-
Pseudomonas organisms.
Methods
Institutional review board approval was obtained for this retro-
spective study (University of Pittsburgh institutional review
board approval #PRO12010268, principal investigator Andrew
A. McCall). The University of Pittsburgh Medical Center
Department of Otolaryngology clinical record database was
searched for all patients diagnosed with MOE between 1995
and 2012. Diagnosis was confirmed by the documented pres-
ence of the all of the obligatory Cohen criteria with 2 modifi-
cations.10 First, it is generally our practice to obtain computed
tomographic (CT) scans in lieu of nuclear medicine studies to
confirm the presence of MOE.11 We therefore included
patients with documented evidence of bony erosion on CT
scans in place of the obligatory Cohen criterion of either posi-
tive results on a technetium-99 scan or failure of local therapy.
Second, because of the retrospective nature of the study, in
some cases, not all of the obligatory clinical criteria were
documented for each patient. We accepted patients into the
present cohort who were missing documentation of no more
than 1 of the clinical signs or symptoms of the obligatory
Cohen criteria, as has been done by others.12 Resolution of
infection was based on the absence of clinical signs or symp-
toms of disease and the absence of radiographic progression of
disease after a minimum follow-up period of 1 month after the
completion of antibiotic therapy. Microsoft Excel 2011
(Microsoft Corporation, Redmond, Washington) and GraphPad
Prism 6 (GraphPad Software, San Diego, California) were
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used for data management and statistical analysis. Statistical
comparisons between groups were performed using Fisher’s
exact test and Student’s t test as appropriate, and statistical sig-
nificance was set at P \ .05.
Results
Demographics
Twenty patients were identified from the database with sup-
porting documentation that permitted confirmation of the
diagnosis of MOE. The mean age at diagnosis was 65 years
for all patients, 62 years for Pseudomonas-infected patients,
and 63 years for MRSA-infected patients. There were 12
men and 8 women (Table 1).
Culture Data
Culture and sensitivity data were documented for all 20
patients. The means of obtaining culture data and therapy
prior to culture are documented in Table 2. There were 9
patients (45%) whose cultures grew P aeruginosa. There
was no documented ciprofloxacin resistance in any of the
Pseudomonas specimens; 1 Pseudomonas isolate was resis-
tant to levofloxacin. Two patients had cultures that grew
methicillin-sensitive S aureus in addition to Pseudomonas.
Three patients (15%) had cultures that grew MRSA in the
absence of Pseudomonas. One patient infected with MRSA
also grew Klebsiella and another grew pan-resistant
Acinetobacter spp. One MRSA isolate was resistant to clin-
damycin; there was no documented resistance to doxycy-
cline, trimethoprim-sulfamethoxazole, or vancomycin.
In the 5 remaining patients with positive cultures, the fol-
lowing organisms were documented (often in a polymicro-
bial fashion): Enterococcus spp (n = 2), methicillin-
sensitive S aureus (n = 1), Candida spp (n = 1), Aspergillus
(n = 1), Staphylococcus lugdunensis (n = 1), Lactobacillus
(n = 1), Peptostreptococcus (n = 1), and Alcaligenes faecalis
(n = 1). Three patients had negative cultures.
Cranial Neuropathies
Thirty-three percent of the Pseudomonas-infected patients
presented with facial nerve palsies, compared with none of
Hobson et al 3

Table 2. Culture Methods and Prior Therapy.

Patient Therapy Prior to Culture Culture Method

Pseudomonas
1 None Canal swab
2 Oral amoxicillin-clavulanic acid and topical ciprofloxacin-dexamethasone Canal swab
3 Unknown Canal swab
4 Unknown Canal swab
5 Oral ciprofloxacin and topical ciprofloxacin-dexamethasone Unknown
6 Oral ciprofloxacin and topical ciprofloxacin-dexamethasone Canal swab
7 Oral antibiotic Unknown
8 Topical antibiotic Canal swab (tissue negative)
9 Oral ciprofloxacin and topical ciprofloxacin-dexamethasone Canal swab
MRSA
10 Oral trimethoprim-sulfamethoxazole Canal swab
11 Topical ciprofloxacin-dexamethasone Canal swab
12 Topical ciprofloxacin-dexamethasone Canal tissue
Other
13 Oral amoxicillin-clavulanic acid and topical ciprofloxacin-dexamethasone Canal swab
14 Oral moxifloxacin and topical ciprofloxacin-dexamethasone Canal swab
15 Topical ciprofloxacin-dexamethasone Canal swab and tissue
16 Unknown Canal swab
17 Oral ciprofloxacin and topical ciprofloxacin-dexamethasone Canal swab and tissue
Negative
18 Oral and topical antibiotics Canal tissue
19 Oral/IV ciprofloxacin and topical ciprofloxacin-dexamethasone Canal swab
20 Topical antibiotic Canal swab
Abbreviations: IV, intravenous; MRSA, methicillin-resistant Staphylococcus aureus.

the MRSA-infected patients and 18% of all non-
Pseudomonas-infected patients. These differences were not
statistically significant (P = .51 and P = .62). No other cra-
nial neuropathies were documented (Table 1).
Comorbidities
Fifteen patients (75%) had diabetes mellitus. All 9 patients
infected with Pseudomonas had diabetes mellitus, compared
with 33% of MRSA-infected patients and 55% of all non-
Pseudomonas infected patients. These differences were statisti-
cally significant (P = .046 and P = .04, respectively). One
patient (non-Pseudomonas, non-MRSA) had acute myeloid leu-
kemia and received chemotherapy at around the time of his
infection; this patient also had diabetes. One patient (non-
Pseudomonas, non-MRSA) had rheumatoid arthritis and was
taking immunosuppressive medications at the onset of infection.
Another patient (non-Pseudomonas, non-MRSA) had systemic
lupus erythematous but was not receiving immunosuppressive
therapy. Overall, 63% of the non-Pseudomonas-infected patients
either had diabetes or were immunosuppressed, compared with
100% of the Pseudomonas-infected patients (P = .09).
Treatment Summary
At the time of this study, 1 patient had an ongoing infection, 3
patients were lost to follow-up, and 1 patient (MRSA, panresis-
tant Acinetobacter) died from a central catheter infection while
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undergoing ongoing therapy for MOE. The remaining 15
patients (75%) had documented resolution of their infections.
Two patients had recurrences of their infections and were
treated with a second course of antibiotics. Of the 15 patients
with documented resolution of their infections, the mean defini-
tive antibiotic course was 7.8 6 3.9 weeks, and the mean total
antibiotic course was 9.2 6 4.2 weeks. The most frequent treat-
ment duration, including treatment of recurrences, was 6 weeks.
Three patients underwent mastoidectomy during their treatment
for MOE: 2 mastoidectomies were performed for patients who,
while receiving intravenous antibiotic therapy, had sequestered
bone in the mastoid seen on CT scans; 1 patient underwent
mastoidectomy to evaluate for malignancy, as that patient exhib-
ited radiographic evidence of progressive bony erosion and a
soft tissue lesion despite treatment.
One of the Pseudomonas-infected patients was lost to
follow-up. The remaining 8 had resolution of their infec-
tions with an average of 6.1 6 2.1 weeks of definitive anti-
biotic therapy and 7.9 6 3.4 total weeks of antibiotic
therapy. Five of those 8 patients were treated with oral qui-
nolone antibiotics, 3 in combination with an intravenous
anti-Pseudomonal cephalosporin. One patient was treated
with intravenous moxifloxacin. The 2 patients who were not
treated with quinolone antibiotics were treated with an intra-
venous anti-Pseudomonal penicillin. One patient, who did
not follow up, underwent a canal wall up mastoidectomy.
4 Otolaryngology–Head and Neck Surgery
Two of 3 MRSA-infected patients had resolution of their
infections, averaging 8.5 6 0.7 weeks of definitive antibio-
tic therapy and 12.6 6 0.9 total weeks of antibiotic therapy.
One patient infected with MRSA and Acinetobacter died
from an infected central catheter while undergoing treatment
for MOE. Although the treatment duration was longer for
MRSA-infected than for Pseudomonas-infected patients,
these differences in duration were not statistically signifi-
cant (P = .18 for total and P = .10 for definitive therapy).
None of the MRSA-infected patients underwent surgical
intervention beyond debridement of the ear canal. The
MRSA-infected patients were treated with intravenous
vancomycin.
Overall, the 7 patients with documented resolution of
non-Pseudomonas infections were treated with antibiotics
for an average of 9.3 6 4.5 weeks of definitive antibiotic
therapy and 10.4 6 4.6 total weeks of antibiotic therapy.
These treatment durations were longer (3.2 and 2.5 weeks,
respectively) than those for the Pseudomonas-infected
patients but did not reach significance (P = .09 and P =
.25). Six of these 7 patients (86%) received intravenous
therapy with nonquinolone antibiotics.
Discussion
Classically, MOE has been thought to be due exclusively to
Pseudomonas infection. In fact, Cohen and Friedman10 sug-
gested the presence of Pseudomonas on cultures as an obli-
gatory diagnostic criterion for this disease, though noting
that this required further investigation. In 1988, Rubin and
Yu3 performed a literature review of 260 cases of MOE and
found that virtually all cases (99.2%) were caused by
Pseudomonas. With increasing frequency, however, non-
pseudomonal cases of MOE are being reported. Fewer than
half (45%) of the patients in our study had cultures that
grew Pseudomonas. Similarly, in 2010, Chen et al7 and
Jacobsen and Antonelli13 reported relatively low proportions
of pseudomonal MOE, with only 26.9% and 34% of their
respective patients having Pseudomonas isolated in cultures.
Commensurate with the decline in Pseudomonas isolates
has been a rise of other organisms leading to MOE.5-7,13
The second most common isolate in our series was S
aureus, with 3 isolates being MRSA (15%). To our knowl-
edge, there are few reports documenting MRSA as a causa-
tive organism in cases of MOE.7,8
With the evolving microbiology of MOE, it is essential
that treatment be tailored to the causative organism(s).
Since its introduction in the late 1980s, oral ciprofloxacin
has commonly been used as a first-line empiric treatment
for MOE.14 This allowed patients with early-stage disease
to be treated empirically in an outpatient setting. Now, how-
ever, with the increasing frequency of nonpseudomonal
MOE, ciprofloxacin may not always be an effective treat-
ment, as it has poor gram-positive coverage and is ineffec-
tive against MRSA.
Additionally, the incidence of ciprofloxacin-resistant
Pseudomonas has been rising. Although there was 1 instance
of levofloxacin resistance and not any documented
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ciprofloxacin resistance in our Pseudomonas isolates, other
investigators have reported an increasing incidence
ciprofloxacin-resistant Pseudomonas as a cause of MOE.14,15
In 2002, Berenholz et al15 were the first to report MOE
caused by ciprofloxacin-resistant Pseudomonas, with 33% of
their Pseudomonas isolates being resistant to ciprofloxacin.
The clinical features of MOE caused by Pseudomonas and
MRSA were similar in many respects (average age of onset,
signs and symptoms, etc), but some important differences
were noted. Diabetes is a commonly noted comorbidity in
patients with MOE and, along with immunocompromised
state, is thought to be a risk factor for development of the
disease.3 In our series, all of the Pseudomonas-infected
patients had diabetes, whereas only 1 of the 3 MRSA-
infected patients did (P = .046). Additionally, only 55% of
the patients with non-Pseudomonas infections had diabetes,
which was also significantly less than in the Pseudomonas-
infected patients (P = .04). These findings illustrate the point
that a diagnosis of MOE must be considered in any patient
with refractory otitis externa, even in those without diabetes.
Furthermore, it suggests that atypical organisms, such as
MRSA, should be suspected in patients without diabetes who
present with MOE.
There were important limitations of this study worth men-
tioning. First, the study was retrospective in nature, and data
were limited to the available records. Additionally, the
patient population was heterogeneous in terms of prior ther-
apy and the manner in which cultures were obtained. It is
possible that prior therapy would eradicate organisms that
would have otherwise have been detected on culture. This
means that potentially pathogenic organisms (in isolation or
as a part of a polymicrobial infection) may have been eradi-
cated or rendered undetectable by culture prior to presenta-
tion to our offices in some instances. Furthermore, ear-swab
culture may not always be reflective of the pathogenic organ-
ism infecting the temporal bone in MOE. Although the spe-
cific role of culture method has not been investigated in
MOE, discordance between swab and bone culture has been
shown for diabetic foot osteomyelitis.16 For this reason, we
recommend tissue biopsy in cases in which there is poor
or no response to ear-swab culture–directed therapy.
Additionally, the choice of antibiotic was based on the
preference of the treating neurotologist in conjunction
with an infectious disease specialist. Many patients were
treated with intravenous antibiotics, while sensitivities sug-
gested that an oral antibiotic could have been used. Because
MRSA is a rare organism to cause MOE, there are few data
guiding treatment of this offending organism. It is worth
noting that 1 of our MRSA-infected patients was being treated
with oral trimethoprim-sulfamethoxazole at the time of presen-
tation and culture. Although sensitivities indicated that the
organism was susceptible to this antibiotic, the patient’s infec-
tion was not responsive to this treatment. The infection was
resolved with intravenous vancomycin treatment.
In general, treatment durations were planned for 6 weeks
and extended as needed on the basis of clinical or radio-
graphic evidence of persistent or progressive disease. It is
Hobson et al
worth mentioning that neither technetium nor gallium scans
were routinely used for diagnosis or monitoring of disease;
thus, it is possible that some patients with clinical and radio-
graphic evidence of resolution may have in fact had ongoing
infections. Finally, because many of our patients travel long
distances for care at our center, they often elect to follow up
with their local otolaryngologists after the completion of
treatment and apparent resolution of their infections. This
precluded us from following outcomes for the majority of
the patients in our study beyond 1 month after the comple-
tion of antibiotic therapy.
Conclusions
Our study underscores the increasing frequency of non-
Pseudomonas causes of MOE and specifically highlights
that MRSA is an increasingly important organism leading to
MOE. A high index of suspicion for atypical organisms,
such as MRSA, should be maintained in patients with signs
and symptoms of MOE who do not have diabetes.
Author Contributions
Candace E. Hobson, Data acquisition and analysis, interpretation
of data, drafting of manuscript, final approval; Jennifer D. Moy,
data acquisition, critical revision of manuscript, final approval;
Karin E. Byers, Study conception and design, critical revision of
manuscript, final approval; Yael Raz, study conception and design,
critical revision of manuscript, final approval; Barry E. Hirsch,
study conception and design, critical revision of manuscript, final
approval; Andrew A. McCall, study conception and design, analy-
sis and interpretation of data, drafting and critical revision of
manuscript, final approval.
Disclosures
Competing interests: None.
Sponsorships: None.
Funding source: None.
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